In the proposed work we will continue an analysis of the proliferation kinetics of gastrointestinal epithelial cells in man, and in rodent after a chemical carcinogen, and compare the evolution of gastrointestinal carcinoma in both. Nucleotide precursor enzyme activites will be analyzed during neoplastic transformation of gastrointestinal cells, and the contribution of abnormal enzyme activities to persistent proliferation will be studied. Differences in regulatory control of cell proliferation and differentiation in regions of colon and stomach susceptible to malignant transformation will be analysed. The data will be correlated with changes in proliferation kinetics to identify with increased precision the stages of development of gastrointestinal neoplasms in man. The development of biochemical and immunological tests to improve the detection of early and late stages of malignancy, and new approaches to chemotherapy will be evaluated.